ADVANCED BREAST CANCER MedDRA version: 14.1 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PD 0332991
Product Code: NA
Pharmaceutical Form: Capsule, hard
Current Sponsor code: PD 0332991
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Sponsors
FONDAZIONE SANDRO PITIGLIANI PER LA LOTTA CONTRO I TUMORI-ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease. 2. ER positive tumor = 10% 3. HER2 negative breast cancer by FISH or IHC (IHC 0,1+, 2+ and/or FISH HER2: CEP17 ratio 60 years; • Age 1 (except alopecia or other toxicities not considered a safety risk for the patient). 10. Adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Unstable brain metastases (stable brain metastases not requiring steroids are allowed); presence of spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. 2. Major surgery within 3 weeks of first study treatment. 3. Prior treatment with: • More than one line of chemotherapy for advanced breast cancer • More than two lines of endocrine treatment for advanced breast cancer • Any CDK inhibitor. 4. Current treatment with: • Any experimental treatment on another clinical trial; • Therapeutic doses of anticoagulant (Low dose anticoagulants for deep vein thrombosis prophylaxis are allowed. Aspirin is permitted.) 5. Current use or anticipated need for: • food or drugs that are known strong CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, tilithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine • drugs that are known strong CYP3A4 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St. John’s Wort) 6. Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. 7. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE grade =2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. 8. Active inflammatory bowel disease or chronic diarrhea. Short bowel syndrome. Upper gastrointestinal surgery including gastric resection. 9. Known hypersensitivity to letrozole, anastrazole, exemestane or fulvestrant, or to any of their excipients. 10. Known human immunodeficiency virus infection; active Hepatitis C, active hepatitis B 11. Severe medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with interpretation of study results and, in the investigator opinion, would make the subject inappropriate for this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the activity of PD 0332991 monotherapy and of PD 0332991 in combination with the endocrine therapy (anastrozole, letrozole, exemestane or fulvestrant) on which the patient has progressed in the previous line (1st or 2nd) for ER+, HER2 negative ABC in post-menopausal women;Secondary Objective: To assess the tolerability of PD 0332991 in combination with anastrozole, letrozole, exemestane or fulvestrant in postmenopausal women with ER+, HER2 negative ABC. To assess secondary measures of activity for PD 0332991 monotherapy and PD in combination with an endocrine therapy. To explore the relationship between copy number and expression of baseline genes of interest and protein levels including Rb, p16/INK4A, CCND1, CDK4, CDK6, and Ki67 markers with tumor response. To explore the relationship between germline polymorphism in CYP19A1 and CCND1 genes and tumor response;Primary end point(s): Clinical benefit (CB) defined as complete response, partial response, and stable disease for at least 24 weeks, according to RECIST criteria 1.1 from randomization to termination of PD 0332991 ± endocrine therapy;Timepoint(s) of evaluation of this end point: Activity assessments will be every 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Adverse events according to CTCAE v4.0 •Objective response (OR) according to RECIST 1.1 •Progression Free Survival. •Time to tumor progression (TTP) •Duration of response (DR). •Overall survival (OS). •Tumor tissue levels including but not limited to Rb, p16/INK4A, CCND1, CDK4, CDK6 and Ki67 and copy number of CCND1 and p16. •Germline polymorphism in CYP19A1 and CCND1 genes;Timepoint(s) of evaluation of this end point: Adverse events will be collected every cycle and activity assessments will be performed every 12 weeks. | — |
Countries
Italy
Contacts
Public ContactOncologia Medica
Azienda USL 4 di Prato
Outcome results
None listed